This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Our goals in this collaboration are to investigate the role of alpha-synuclein and hydroxybutyrate dehydrogenase type 2 (BDH2) in the progression of Parkinson disease (PD) and assess putative therapeutic strategies. We intend to apply the tetracysteine (4Cys)-labeling system developed at NCMIR to track, at multiple resolution scales, the trafficking of proteins associated with PD. This work will draw upon the techniques being advanced at NCMIR, including improved 4Cys approaches, correlated live imaging-3D electron microscopic analysis, and high-resolution electron tomographic reconstruction.